| Summary: | The most commonly used regimens fail to eradicate <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection in 5⁻10% of patients. Those not cured with treatments based on amoxicillin, clarithromycin, nitroimidazoles, fluoroquinolones, bismuth or tetracycline have no other conventional options thereafter. In this prospective long-term monocentric study, patients who failed to eradicate <i>H. pylori</i> following treatment with all conventional antibiotics were included. All subjects were treated with rifabutin 150 mg, amoxicillin 1 g and a standard dose of proton pump inhibitor, twice daily for 14 days. A negative <sup>13</sup>C-urea breath test was used four weeks after treatment completion as an index of <i>H. pylori</i> eradication. Three hundred and two patients were included. Fifty-four percent (164/302) had peptic ulcer disease while 45.7% (138/302) had gastritis or functional dyspepsia. Per-protocol eradication and intention-to-treat eradication were achieved in 72.7% and 71.5%, respectively. A univariate analysis showed that gender, ethnic background, smoking habits and familial history of gastric diseases were not predictive factors of response, while with multiple logistic regression analysis, the ethnic background (Italian) predicted a poor response in the second period of the study (2010⁻2017). In conclusion, this study on a large cohort of very difficult-to-treat patients showed that rifabutin-based rescue therapy is an acceptable and safe strategy after multiple eradication failures with conventional antibiotics.
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